Visfatin has recently been identified as a novel visceral adipokine which may be involved in obesity-related vascular disorders. However, it is not known whether visfatin directly contributes to endothelial dysfunction. Here, we investigated the effect of visfatin on vascular inflammation, a key step in a variety of vascular diseases. Visfatin induced leukocyte adhesion to endothelial cells and the aortic endothelium by induction of the cell adhesion molecules, ICAM-1 and VCAM-1. Promoter analysis revealed that visfatin-mediated induction of CAMs is mainly regulated by nuclear factor-kappaB (NF-kappaB). Visfatin stimulated IkappaBalpha phosphorylation, nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA binding activity in HMECs. Furthermore, visfatin increased ROS generation, and visfatin-induced CAMs expression and NF-kappaB activation were abrogated in the presence of the direct scavenger of ROS. Taken together, our results demonstrate that visfatin is a vascular inflammatory molecule that increases expression of the inflammatory CAMs, ICAM-1 and VCAM-1, through ROS-dependent NF-kappaB activation in endothelial cells.

To provide a basis for studying the molecular mechanism of pharmacological action of local anesthetics, we carried out a study of the membrane actions of tetracaine, bupivacaine, lidocaine, prilocaine and procaine. Fluorescence polarization of 12-(9-anthroyloxy)stearic acid (12-AS) and 2-(9-anthroyloxy)stearic acid (2-AS) were used to examine the effects of local anesthetics on differential rotational mobility between polar region and hydrocarbon interior of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. The two membrane components differed with respect to 2 and 12 anthroyloxy stearate (2-AS, 12-AS) probes, indicating that a difference in the membrane fluidity may be present. In a dose-dependent manner, tetracaine, bupivacaine, lidocaine, prilocaine and procaine decreased anisotropy of 12-AS in the hydrocarbon interior of the SPMV, SPMVTL and SPMVPL, but tetracaine, bupivacaine, lidocaine and prilocaine increased anisotropy of 2-AS in the membrane interface. These results indicate that local anesthetics have significant disordering effects on hydrocarbon interior of the SPMV, SPMVTL and SPMVPL, but have significant ordering effects on the membrane interface, and thus they could affect the transport of Na(+) and K(+) in nerve membranes, leading to anesthetic action.

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mimicking WT and CIP resistant J774 cells, by fluorescence polarization spectroscopy. In this respect, we observed a decrease in the melting temperature in vesicles mimicking the membrane composition of CIP resistant cells, indicating that changes in the fluidity of these membranes may be due to the decrease of SM. Studies are currently performed to investigate potential changes in other components of rafts like glucosylceramides. These data might have important relevance to relate the interaction of fluoroquinolones with lipids and change in the processes involved in cellular accumulation of fluoroquinolones.

A high level of cholesterol in the blood is associated with predisposition for cardiac diseases and is one of the major human health problems [1]. Some cholesterol is synthesized in the liver and a significant amount is also absorbed from dietary cholesterol at the small intestinal brush border membranes. Dietary cholesterol is first emulsified in mixed micelles of bile salts (BS) and fatty acids (FA) and the currently accepted mechanism suggests that absorption involves the interaction between the mixed micelles and the apical membrane of brush border cells where passive mechanisms play a significant role [2]. However, the detailed mechanism and the dependence on the dietary mixture of lipids are far from being completely understood. In most studies, mixtures of BS and FA have been used and the distribution of cholesterol between different phases and/or the in vitro cholesterol intake has been measured [3]. The complexity of the systems studied precludes the interpretation of the effect of each component in the process. Here we present the study of the solubilization of a cholesterol analogue, Deydroergosterol, in micelles of glycocholic acid and glycochenodeoxycholic acid (most abundant BS in the upper intestine[3]) followed by fluorescence. We develop a kinetic model to describe the rate of sterol emulsification and its maximum solubility in the BS micelles. The study was also performed with cholesterol labeled with C13 in carbon 4 in the sterol ring and followed by C13 NMR Spectroscopy. From preliminary results we can identify and quantify the emulsified cholesterol in the BSM at a chemical shift of 41.6 ppm that is well separated from the C13 NMR resonances of BS [4]. From the data obtained we obtain the cholesterol saturation index and the kinetic profile for the solubilization of cholesterol in the BS micelles.